112 PROTEIN THERAPY 



may be a chill, the temperature rises sharply and instead of dropping 

 after a few hours, as it would in an ordinary infectious case, stays 

 high for from 24 to 48 hours. Usually this reaction is accompanied 

 by general malaise and every indication of increased inflammatory 

 reaction about the tumor. After this period the temperature drops, 

 the patient feels better than before the injection, gains in weight, 

 pain is lessened and retrogressive changes are noted in the 

 tumor. It has been shown that following such an injection of 

 a nonspecific agent a definite shifting of the ferment-antiferment 

 balance takes place so that the antiferment is lessened and the 

 activity of the protease increased. At the tumor site this means that 

 this protease begins to digest some of the native proteins of the 

 necrotic debris. Toxic split products are liberated, they diffuse 

 out from the focus into the surrounding healthy tissue, cause irri- 

 tation, the attraction of leukocytes, vascular engorgement, increased 

 tension and with it increased pain. It is during this period of 

 absorption of the soluble split products that the febrile period and 

 systemic effect of a general malaise are observed. The leukocytes 

 attracted by the digestive inflammatory reaction partly succumb, 

 partly migrate from the field. A certain amount of leukoprotease is 

 certainly liberated from them. During this period, too, we have an 

 increase in the amount of nitrogen excreted i.e., a negative balance. 

 Then follows the period of recovery of the balance and the change 

 to the reparative side. The antiferment is increased over the amount 

 present before the injection; the protease action is checked, in- 

 creased amounts of ereptase make their appearance and detoxicate 

 whatever remnants of split products still remain near the focus. 

 During this period the patient manifests every sign of clinical im- 

 provement euphoria, increase of weight, appetite, etc. The in- 

 crease of weight that follows the increase in the antiferment curve 

 has been worked out in a series of clinical conditions by Breed. 



The tumor in the meantime may have actually decreased in size 

 by the effects of the reaction because a certain amount of necrotic 

 material has been digested away. It is of course evident that the 

 living tumor cells need in no way be susceptible to the effect of the 

 enzymes and that the reaction, as far as a matter of cure is con- 

 cerned, is not to be regarded as a therapeutic agent for such malig- 

 nant conditions. It may have a place in the therapy of malignant 

 conditions if by producing an inflammatory reaction repeatedly we 

 can, either by cellular or vascular changes, aid in the resistance of 

 the body to the neoplastic invasion (Theilhaber) . Until we have 

 certain knowledge of these factors in tumor growth we must un- 

 fortunately deal more or less empirically with the conditions. Nor 

 must it be forgotten that the inflammatory reaction that is brought 

 about may at times not be helpful but may actually stimulate the 

 tumor cells to greater activity and malignancy, and therefore be of 



